These investigations are concerned with the processes and control of lymphoid differentiation, beginning with multipotential stem cells and ending with the mature T and B lymphocytes which mediate immune defense. An important part of these studies is to compare and contrast normal differentiation with the defects which occur in malignancy and in immunodeficiency diseases. Using organ and cell culture techniques we will attempt to define discrete steps in B-cell differentiation from stem cells to mature lymphocytes. These studies will depend on the use of markers to identify stages of B cell differentiation, including pre-B cells and immature B cells, and on correlation of markers with functional activity. B lymphoma cells will be compared with normal lymphocytes as regards mobility of cell-membrane receptors and differentiation capacity when stimulated by mitogens. These studies will be performed using human lymphomas and the avian lymphoid leukosis model. Using recently developed assays, we will study the capability of subpopulations of human T cells to either help or suppress B-cell differentiation induced by pokeweed mitogen. T cells will be fractionated on the basis of receptors for the Fc portion of IgM and IgG immunoglobulins. The presence of these markers will also be sought on leukemic lymphocytes. BIBLIOGRAPHIC REFERENCES: Raff, Martin C., Owen, John J.T., Cooper, Max D., Lawton, Alexander R., III, Megson, Mary, and Gathings, Bill: Differences in susceptibility of mature and immature mouse B lymphocytes to anti-immunoglobulin induced immunoglobulin suppression in vitro: Possible implications for B cell tolerance to self. J. Exp. Med. 142:1052-1064, 1975. Owen, J.J.T., Raff, M.C., and Cooper, M.D.: Studies on the generation of B lymphocytes in mouse embryo. Eur. J. Immunol. 5:468-473, 1975.